Friday May 31, 2013 (8.00 – 16.30)

    08:00 Registration

     09:00 Opening ceremony

      100th Anniversary of the Clinical Department of Pathology “Ljudevit Jurak”

                Marina Kos (Zagreb, Croatia): Professor Ljudevit Jurak: to die for the truth

     09:45 – 10:00 Coffee break

PATHOLOGY OF HUMAN AND ANIMAL DISEASES

Invited lectures - Chair persons: G.Vujanić, M. Kos, B. Krušlin

     10:00 Ondrej Hes (Plzen, Czech Republic):

                   Adult kidney tumors: new emerging entitiesbeyond WHO classification 2004.

     10:40 Discussion

     10:50 Slide seminar cases.

     11:10 Michal Michal (Plzen, Czech Republic):

               Renal cell neoplasms with epithelial and stromal components.

     11:50 Discussion

     12:00 Slide seminar cases.

     12:20 – 13:00 Coffee break

Invited lectures - Chair persons: O. Hes, F. del Piero, M. Michal

     13:00 Heinz Regele (Innsbruck, Austria):

               Kidney allograft pathology: from morphology to function.

     13:40 Discussion

     13:50 Slide seminar cases

     14:10 Danica Galešić-Ljubanović (Zagreb, Croatia):

                Epidemiology of renal diseases in Croatia: registry of renal biopsies from the

                Department of Pathology Dubrava University Hospital

     14:50 Discussion

     15:00 Slide seminar cases.

     15:20 – 15:40 Coffee break

     15:40 General Assembly of Croatian Society of Patho logy and Forensic Medicine

     20:00 Get together dinner

 

Saturday June 1st, 2013 (9.00 – 15.00)

PATHOLOGY OF HUMAN AND ANIMAL DISEASES

     09:00 Gregor Mikuz (Innsbruck, Austria) – Quiz on histopathology

     10:00 – 10:20 Coffee break

Invited lectures - Chair persons: G. Mikuz, H. Regele, Ž. Grabarević

     10:20 Gordan Vujanić (Cardiff, UK):

                Pathology of renal tumours of childhood - a review.

     11:00 Discussion

     11:10 Slide seminar cases.

     11:30 – 12:00 Coffee break

     12:00 Fabio del Piero (Louisiana, USA):

                Infectious diseases of kidneys in animals.

     12:40 Discussion

     12:50 Slide seminar cases.

     13:10 Suzana Tkalčić (Pomona, CA, USA):

                Zoobiquity® in renal pathology: animal and human interface.

     13:50 Discussion

     14:00 Slide seminar cases.

     14:20 – 14:30  Short break

     14:30 Award for the best poster and “Dr. Suzana Tkalčić ONE HEALTH Award”

Closing ceremony

 LECTURES

All lectures in pdf

PROFESSOR LJUDEVIT JURAK – TO DIE FOR THE TRUTH

Marina Kos

Clinical Department of Pathology „Ljudevit Jurak“, Clinical Hospital Center „Sestre milosrdnice“, Institute of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia

Ljudevit Jurak was born in the village of Zalug on the 6^th October 1881. He frequented the elementary school in the nearby village Prišlin, and he continued his education in Zagreb. He graduated from high-school with honours and merited a scholarship to continue his education at the Medical School of Innsbruck University where he graduated in 1910. The medical career of doctor Jurak began at the Department of Pathology of the University of Innsbruck Medical School, where he became an assistant to prof. Pomer in 1911. He specialized in pathology and anatomy until 1914, and he also cooperated with prof. Ipsen from the Institute of Forensic Medicine in Innsbruck. His education in veterinary pathology continued at the Vienna University and Dresden University School of Veterinary Medicine with prof. Hartl and prof. Joest. The field of his special interest was the conductive system of the heart in embryos, children and adults and he published an article on this topic in Wiener klinische Wochenschrift in 1914. He also investigated pathological changes in syphilis in the aorta and the blood vessels of the brain and meninges. Together with assistant professor doctor Felix Gaisbock, he published an article entitled „Klinische und anatomischhistologische Untersuchungen uber einen Fall mit Adams-Stokes'schem Symptomenkomplex“ in Zentralblatt fur Herz und Gefasskrankheiten.

In 1913. he accepted the position of prosector (coroner) for all the hospitals in Zagreb including the mental institution in Stenjevec. He became professor of general pathology and veterinary pathology in 1921, the dean (1929/30 and 1937/38) and vice-dean (1938/39) of School of Veterinary Medicine of Zagreb.

In the academic year 1917/18 the Medical School was founded in Zagreb. During the period of 1922 -1932 dr. Jurak was a professor of forensic medicine. The interesting fact is that he autopsied the Croatian politician Stjepan Radić after his assassination in 1928.

The faith of prof. Jurak is closely associated with the historical events of that time, precisely with the political and ethnic cleansing done by the infamous NKVD in the Soviet Union during Stalin's government. Except for the widely known execution of Polish army officers in the Katyn forest in 1940., the Soviet goverment conducted mass executions of peasants in Ukraine. One of the places where mass executions were performed was the ukrainian village of Vinnytsa. After The Nazi Germany occupied those parts of the Soviet Union, mass graves where discovered, and the German propaganda wanted to use these discoveries against the communists. To prove that the discovered bodies were civilians executed by shooting, and not the enemy soldiers killed in combat, the commission was formed to investigate and evaluate the findings. The first commission consisted of German, Ukrainian and Russian doctors, and it discovered 91 mass graves with 9432 bodies. After that, two other commissions were formed: the first were 13 authorities from the different universities in Germany, ant the members of the second were 11 well recognized medical authorities in anatomy and forensic medicine from Belgium, Bulgaria, Finland, France, Italy, Netherlands, Romania, Sweden, Slovakia, Hungary and Croatia. The member from Croatia (at that time Independent State of Croatia) was prof. Ljudevit Jurak. The international commission visited the mass graves between July 13^th and July 15^th, 1943, and completed the report on the July 29^th, 1943. Both commissions determined that almost all of the victims were executed by two shots in the back of the head between 1937–1938.

Upon his return to Croatia, prof. Jurak described the findings in the article “Mass graves in Vynnitsa” (Skupni grobovi u Vinici), published in the newspapers “Croatian people” (Hrvatski narod) in 1943. After the end of the Second World War, the Federal Republic of Yugoslavia was formed, and the new communist government (on the order by NKVD) arrested prof. Jurak on the 15^th May 1945. Based upon the article in the newspapers, he was accused of war crimes committed by the foreign occupation forces and their collaborators. The explanation was that he participated in the so called International Committee which was instructed by German Ministry of Foreign affairs and Ministry of Health to attribute the mass slaughter of Vinnytsa, by using their allegedly scientific knowledge, to the Bolshevik authorities and by emphasizing that victims were civilians - mostly peasants and working class people (in contrast to victims of Katyn forest who were Polish officers) to spread, maliciously and intentionally, fear and hatred towards the Soviet Russia in our peasants and working class. He published tendentious photographs of the excavation site, and by all that he deliberately and maliciously propagandized against friendly Soviet Russia, and therefore indirectly against our people. Thus he committed a crime from article 13 of the Military Courts Act.

Prof. Jurak was offered to renounce his statements about Vinnytsa and withdraw his signature on the report by saying he gave them under compulsion, and he would be pardoned in return. He refused to do it. Therefore, he was found guilty of all crimes described above, and sentenced to death by shooting, permanent loss of citizen's honours, and confiscation of property.

The most interesting fact is that the verdict was typed up even before the arrest warrant. The verdict (9^th June) is dated before the arrest warrant (9^th July). Obviously, his fate was determined long before the trial.

The Soviet Union claimed the victims had been murdered by the Nazis, and continued to deny responsibility for the massacres until 1990, when it officially acknowledged and condemned the perpetration of the killings by the NKVD, as well as the subsequent cover-up.

In 1990. on the initiative of Prof. Mladen Belicza and Prof. Križan Čuljak the Dpts. of Pathology of the Veterinary Faculty of Medicine and Clinical Hospital “Sestre milosrdnice” in Zagreb established an annual international memorial symposium on comparative pathology dedicated to prof. Jurak. In 1991. The Dpt. of Pathology at the Clinical Hospital (now Clinical Hospital Center) “Sestre milosrdnice” was renamed Clinical Department of Pathology “Ljudevit Jurak”, and in 1998. The "Ljudevit Jurak" Award for Comparative Pathology was created, whith the goal to encourage scientists from different counties to compare animal and human diseases and remember prof.Jurak's contribution to the medical, forensic and veterinary sciences and to medical ethics.

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NEWLY DESCRIBED RENAL TUMORS OF ADULTS BESIDES WHO 2004

Ondrej Hes

Sikl's Department of Pathology, Charles University Hospital and Medical Faculty, Plzen, Czech Republic

SDHB mutations associated renal tumors

Germline succinate dehydrogenase B (SDHB) mutation causes pheochromocytoma/paraganglioma syndrome type 4. For diagnosis the following is important: morphology (mostly oncocytic tumors with entrapped renal tubuli and bubble-like cytoplasm) + negative SDHB staining + molecular genetic analysis. Patients should be examined for inherited familial trait. Although prognosis is usually favorable, sarcomatoid differentiation exists.

Translocation t(6,11) associated renal cell carcinoma (RCC)

Approximately 30 cases published; M:F 3:8, mean age 27.1 years. Clinically: usual symptoms or asymptomatic. Mean size of the tumors 68 mm. Mean follow up 17 months. Only 2 aggressive cases with metastatic activity are known in the literature. Pseudorosette formations are typical, however, could be scarce and inconspicuous. Typically HMB45 positive. Cytokeratins originally described as negative, however, tumors are positive for several cytokeratins (+++ OSCAR, ++AE1-AE3, patchy CAM5.2 positivity), EMA negative, mostly cathepsin K +++.

Argani et al. have published an interesting study, showing that the occurrence of small areas morphologically almost identical to ASPL-TFE3 translocation renal carcinomas within rosette forming renal carcinoma is possible and not uncommon.

• The MiT subfamily of transcription factors includes TFE3, TFEB, TFEC, and MiTF. Gene fusions involving two of these factors have been implicated in RCC.

• Both Xp11.2 and t(6;11) tumors are considered as members of MiTf

ACRD-associated RCCs

Two papers report similar results independently: Sule et al. in Am J Surg Pathol (12/2006) and Tickoo et al. again in Am J Surg Pathol (1/2006).

Originally, two different types of renal tumors have been described. However, only one type is considered to be so-called ACRD-associated RCC. The tumor is characterized by cells with eosinophilic cytoplasm, cribriform/sieve-like architecture, and intratumoral oxalate crystals. At the 2012 ISUP consensus conference, 91% of respondents thought that ACD-RCC should be recognized as a distinct renal cell tumor entity.

Tubulocystic RCC

Usually, cases were limited to the kidney. Distant metastases from LGCDC have been reported as well as regional lymph node involvement. Size range: 0.2-17 cm, age 34-94 (mean 60) years. Strong male predominance: M/F 7:1. Mostly tubular or microcystic architecture. Cells are usually eosinophilic to oncocytic, variably shaped. Immunohistochemically: CD15, EMA, racemase, CK 7 positive. Occasionally CD10, CAM 5.2 positive. aCGH: gains of chromosomes 7 and 17p, 17q (trisomy/polysomy). Mostly low-grade, low-stage tumor.

Relationship with PRCC is usually discussed: tubulocystic RCC could contain small foci of well-demarcated, well-differentiated PRCC, both lesions have similar IHC and molecular-genetic profile. Differential diagnosis: vs urothelial lesion, vs "real" collecting duct carcinoma, vs papillary RCC, vs mixed epithelial and stromal tumor of the kidney, vs metastasis.

Thyroid-like follicular RCC

Mostly occurring in young women. Only 1 case with metastasis in regional lymph node. Size ranged from 1.9-11.8 cm. Tumors resemble parenchyma of thyroid gland or postpyelonephritic scar within kidney parenchyma. Immunohistochemistry: positive for AE1-AE3, CD 10, vimentin. Negative for TTF1, thyroglobulin, CEA, K903, CK7, CK19, CK20, EMA. Molecular-genetic profile (genomic changes analyzed in one case): gains of 7q36, 8q24, 12,16, 17p11-q11, 17q24, 19q, 20q13, 21q22.3, Xp. Losses of 1q36, 3, 9q21-33. Differential diagnosis: vs metastasis of thyroid carcinoma (positivity for thyroglobulin, TTF1), vs primary or secondary teratoma of the kidney (sampling, gain of 12p).

Hereditary leiomyomatosis associated RCC

Hereditary leiomyomatosis associated renal cell carcinoma (HLRCC) is not a “new” entity and indeed it was described in the 2004 WHO classification of renal neoplasms in the section related to hereditary renal cell carcinoma. Nevertheless, at that time it was not listed as a distinct subtype of renal cell carcinoma and there was a suggestion that HLRCC was a hereditary counterpart of type II PRCC. It is now known that HLRCC, while usually having a papillary pattern, is a tumor with an aggressive behaviour and as such should be recognized as a distinctive subtype.

Hybrid oncocytic/chromophobe RCC

Heterogeneous group with provisional name. During Vancouver ISUP consensus conference, HOCTs were designated as a subtype of chromophobe RCC. Three basic clinicopathologic settings exist:

- within renal oncocytosis/oncocytomatosis (frequently associated with chromophobe RCC),

- within setting of Birt-Hogg-Dubé syndrome (autosomal dominant disorder: multiple fibrofolliculomas in the head and neck region and upper trunk area, increased risk of the development of renal neoplasia and spontaneous pneumothorax), and

- sporadic cases.

Morphology is overlapping between renal oncocytoma and chromophobe RCC. Immunohistochemically, tumors are positive for AE1-AE3, EMA, antimitochondrial antigen, CK7, E cadherin, parvalbumin. Vimentin is strongly but focally (few cells) positive. Mostly negative for racemase, CK20, CD10, CANH IX. Molecular-genetic features:

sporadic HOCTs are characterized by multiple numerical aberrations (both mono- and polysomies), namely of chromosomes 1, 2, 6, 9, 10, 13, 17, 20, 21, 22. Monosomy of chromosome 20 was the most common numerical aberration, followed by monosomy for chromosome 6 and 9.

Oncocytosis: tumors usually show no chromosomal losses of chromosomes 1, 2, 6, 10, 17. However, losses of chromosomes 1, 14, 21 and Y were seen.

BHD: multiple abnormalities have been reported affecting chromosomes 2, 3, 4, 5, 6, 13 and 18. FLCN gene mutations!!!

ALK-positive RCC

Chromosomal rearrangements involving the anaplastic lymphoma kinase gene (ALK) at 2p23 result in fusion with various partner genes leading to aberrant production of oncogenic protein products in multiple tumor types. ALK rearrangements were identified in RCCs. ALK copy number gain was identified in RCCs. In clear cell RCC, ALK copy number gain was significantly associated with tumor size (P=0.02) and nuclear grade (P<0.001), and with a worse 10-year cancer-specific survival (Sukov et al.). Any benefit from ALK inhibitor treatment???

 

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RENAL NEOPLASMS WITH EPITHELIAL AND STROMAL COMPONENTS

Michal Michal

Sikl's Department of Pathology, Charles University Hospital and Medical Faculty, Plzen, Czech Republic

In this lecture I am going to deal with two entities, mixed epithelial and stromal tumor of the kidney and angiomyoadenomatous tumor.

Mixed epithelial and stromal tumors

Mixed epithelial and stromal tumor of the kidney was first described as an entity by Michal and Syrucek in 1998 (17). In 2000 Michal suggested a concept encompassing a group of renal tumors occurring exclusively in perimenopausal women and composed of spindle cell stroma and variously large glandular structures ranging from small hardly luminized tubules to small cystic structures layered by hobnail-shaped epithelium typical of collecting ducts (18). Four months after this report Adsay et al suggested practically the same concept (2). MESTKs had been published under the following different names in the older literature: leiomyomatous renal hamartoma (1), congenital type of mesoblastic nephroma in an adult (5,7), cystic hamartoma of renal pelvis (when they bulged into the renal pelvis) (16,21), solitary multilocular cyst of the kidney (9), multilocular renal cyst with Műllerian-like stroma (23), and we think that the tumor published recently under the name “adult metanephric stromal tumor” might represent another example of MESTK (6).

MESTK is composed of solid and cystic areas composed of spindle cell stroma and tubules or cystically dilated glands, which are often lined by hobnail cells with an eosinophilic cytoplasm. The stroma is morphologically and immunohistochemically indistinguishable from ovarian stroma. These tumors occur almost exclusively in perimenopausal women. The age and sex of the patients points to the importance of the hormonal milieu in their pathogenesis. The cases of MESTK with a benign morphology usually behave in a benign fashion. They usually do not recur or metastasize (3). The only exception is the report by Levine, who experienced recurrence of a case, which he called “mesoblastic nephroma”, but which is probably an example of MESTK 21 year after the excision (14). Svec et al described the first patient with MESTK, which underwent a malignant change (24).

Interesting is the relationship of MESTK and cystic nephromas. Eble and Bonsib (11) suggest that cystic nephroma is not one but two diseases, and this position seems well-substantiated. Cystic nephroma in adults occurs with 8:1 predominance in women, while cystic nephroma in children occurs more often in boys (15). Cystic nephroma in children forms a continuous spectrum with cystic partially differentiated nephroblastoma (13). Adult type of cystic nephroma practically does not occur before the age of 30, whereas cystic partially differentiated nephroblastoma is exceptional over the age of 2 years. Skeletal muscle fibers are common in cystic partially differentiated nephroblastoma but are not present in cystic nephroma. If cystic nephroma in adults were a terminally differentiated variant of cystic partially differentiated nephroblastoma, it would be remarkable that the skeletal muscle should disappear along with the immature elements. It is interesting to note that similar cystic tumors with ovarian-like stroma do not occur only in the kidney. In fact we think that MESTK represent the renal counterpart of the similar tumors in the biliary tract and pancreas (8,10). In pancreas these tumors with mesenchymal ovarian-like stroma are called “mucinous cystic tumors of pancreas” (3,25). Like the renal counterparts these hepatic and pancreatic tumors immunohistochemically express estrogen receptors and the stroma reveals widespread smooth muscle actin positivity and focally desmin.

In our view, cystic nephroma is a cystic variant of MESTK (19).

Congenital mesoblastic nephroma differs from MESTK in many ways. It affects both sexes, and it occurs nearly exclusively in early childhood. Mesoblastic nephromas are purely mesenchymal tumors. In congenital mesoblastic nephromas, tumor derived epithelial structures are not a typical component of the neoplasm (4). Commonly, entrapped tubules and glomeruli are seen encased within the infiltrative neoplasm. The infiltrative neoplasm may induce metaplastic changes in the entrapped epithelial structures and in adjacent epithelium (20), and seldom exhibit cystic change (12). In contrast, MESTKs are characterized by an intimate relationship of epithelial and stromal elements, both of which appear neoplastic. The infiltrative pattern so typical of mesoblastic nephromas is lacking in MESTKs. In addition, congenital mesoblastic nephroma is known to harbor ETV6-NTK3 gene fusion (22). No such gene fusion was found in 7 cases of MESTKs. Owing to the differences in clinical settings, morphology, and molecular differences, we believe that MESTK and congenital mesoblastic nephroma are two entirely different tumors. Thus the term “adult type of mesoblastic nephroma” should be discarded.

 

References:

1. Abaitua J, Val Bernal JF (1975) Hamartoma leiomyomatoso renal del adulto. Segundo caso de la literature. Arch Esp Urol 26:601-612Adsay NV, Eble JN, Srigley JR, Jones EC, Grignon DJ (2000) Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 24:958-970
2. Adsay NV, Longnecker DS, Klimstra DS (2000) Pancreatic tumors with cystic dilatation of the ducts: intraductal papillary mucinous neoplasms and intraductal oncocytic papillary neoplasms. Semin Diagn Pathol 17:16-30
3. Bisceglia M, Carosi I, Vairo M, Zaffarano L, Bisceglia M, Creti G (2000) Congenital mesoblastic nephroma: report of a Case with review of the most significant literature. Pathol Res Pract 196:199-204
4. Block NL, Grabstald HG, Melamed MR (1973) Congenital mesoblastic nephroma (leiomyomatous hamartoma): first adult case. J Urol 110:380-383
5. Bluebond-Langner R., Pinto PA, Argani P, Chan TY, Halushka M, Jarrett TW (2002) Adult presentation of metanephric stromal tumor. J Urol 168:1482-1843
6. Bouvier R, Beurlet J, Roux MG. Mesoblastic nephroma in adults. Apropos of a case and review of the literature (1996) Arch Anat Cytol Pathol 44:37-41
7. Compagno J, Oertel JE (1978) Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol 69:573-580
8. Davila RM, Kissane JM, Crouch EC (1992) Multilocular renal cyst. Immunohistochemical and lectin-binding study. Am J Surg Pathol 16:508-514
9. Devaney K, Goodman ZD, Ishak KG (1994) Hepatobiliary cystadenoma and cystadenocarcinoma. A light microscopic and immunohistochemical study of 70 patients. Am J Surg Pathol 18:1078-1091
10. Eble JN, Bonsib SM (1998) Extensively cystic renal neoplasms: cystic nephroma, cystic partially differentiated nephroblastoma, multilocular cystic renal cell carcinoma, and cystic hamartoma of renal pelvis. Semin Diagn Pathol 15:2-20
11. Ganick DJ, Gilbert EF, Beckwith JB, Kiviat N (1981) Congenital cystic mesoblastic nephroma. Hum Pathol 12; 1039-1043
12. Joshi VV, Beckwith JB (1989) Multilocular cyst of the kidney (cystic nephroma) and cystic, partially differentiated nephroblastoma. Cancer 64:466-479
13. Levin NP, Damjanov I, Depilis VJ (1982) Mesoblastic nephroma in an adult patient: recurrence 21 years after removal of the primary lesion. Cancer 49:573-577
14. Madewell JE, Goldman SM, Davis CJ, Hartman DS, Feigin DS, Lichtenstein JE (1983) Multilocular cystic nephroma. A radiographic-pathologic correlation of 58 patients. Radiology 146:309-321
15. Mensch LS, Trainer TD, Plante MK (1999) Cystic hamartoma of the pelvis: a rare pathologic entity. Mod Pathol 12:417-421
16. Michal M, Syrucek M (1998) Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract; 194:445-448
17. Michal M (2000) Mixed epithelial-stromal tumors of kidney. Pathol Res Pract 196:275-276
18. Michal M, Hes O, Kuroda N, Kazakov DV, Petersson F, Hora M (2010) What is a cystic nephroma? American Journal of Surgical Pathology 34: 126-127
19. Murphy WM, Beckwith JB, Farrow GM (1994) Tumors of the kidney, bladder and related urinary structures. In Rosai J, Sobin LH, eds. Atlas of Tumor Pathology, vol 11, Washington D.C.: Armed Forces Institute of Pathology
20. Pawade J, Soosay GN, Delprado W, Parkinson MC, Rode J (1993) Cystic hamartoma of the renal pelvis. Am J Surg Pathol 17:1169-1175
21. Rubin BP, Chen CJ, Morgan TW, Xiao S, Grier HE, Kozakewich HP, Perez-Atayde AR, Fletcher JA (1998) Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am J Pathol 154:1451-1458
22. Steele R, Daroca PJ, Hill S, Reed RJ, Thomas R (1994) Multilocular renal cyst (cystica nephroma) with Müllerian-like stroma. Urology 43:549-553
23. Svec A, Hes O, Michal M, Zachoval R (2001) Malignant mixed epithelial and stromal tumor of the kidney. Virchows Arch 439:700-702
24. Thompson LD, Becker RC, Przygodzki RM, Adair CF, Heffess CS (1999) Mucinous cystic neoplasm (mucinous cystadenocarcinoma of low-grade malignant potential) of the pancreas: a clinicopathologic study of 130 cases. Am J Surg Pathol 23:1-16

Angiomyoadenomatous tumor of the kidney

When we published the first case of this entity in 2000, we had not found any similar case published in the literature prior to our publication (). In 2009 we published our additional experience with 5 cases (2). We have currently experience with nearly 40 cases of this tumor. In 2009 we showed that angiomyoadenomatous tumor has monosomies in chromosomes 1, 11 and 16 (3). To the best of our knowledge, no renal tumors show the combination of abnormalities of chromosomes 1, 11 and 16 on FISH. Tumorous cells of clear cell renal cell carcinoma (RCC) often have loss of 3p including 3p13p14, 3p 21.3 and 3p24pter. In papillary RCC, neoplastic cells were generally known to show gain of chromosomes 7, 17, 12, 16 and 20, and loss of chromosome Y. Chromophobe RCC generally exhibits monosomy of chromosomes 1, 2, 6, 10, 13, 17 and 21. In collecting duct carcinoma, neoplastic cells had polysomy of chromosomes 3, 7 and 17, although the histological features were not described in that study. Neoplastic cells of mucinous tubular and spindle cell carcinoma demonstrate monosomy of chromosomes 15 and 22 and, furthermore, disomy or polysomy of chromosomes 7 and 17. Monosomy of chromosomes 1, 3, 4, 6 and 9 has also been reported. Renal oncocytoma shows loss of chromosomes Y and 1, normal chromosome or non-specific results. In metanephric adenoma, gain of chromosomes 7 and 17 and loss of sex chromosome may be seen, but some reports are inconsistent with this result.

Recently several groups of pathologists speculated that angiomyoadenomatous tumor may form part of spectrum of clear cell papillary renal cell carcinomas (4,5,6). We think that, although this possibility cannot be refuted, it is still rather premature to group angiomyoadenomatous tumor with this entity, because very little is known about the genetic profile of these two tumors. In addition, none of our cases ever recurred and none caused metastatic disease.

 References:

1.  Michal M., Hes O., Havlíček F.: Benign renal angiomyoadenomatous tumor. Ann Diagn Pathol 2000: 4:311-315. 
2. Michal M., Hes O., Nemcova J., Sima R., Kuroda N., Bulimbasic S., Franco M., Danis D., Kazakov D.V., Ohe C., Hora M.: Renal angiomyoadenomatous tumor: morphologic, immunohistochemical and molecular genetic study of a new entity. Virchows Archiv 2009: 454: 89-99
3. KurodaN., Michal M., Hes O., Taguchi T., Tominaga A., Mizobuchi K., Ohe C., Sakaida N., Uemura Y., Shuin T., Lee G.H.: Renal angiomyoadenomatous tumor: fluorescence in situ hybridization study. Pathol Internat 2009:59: 689-691 
4. Aydin H, Chen L, Cheng L, Vaziri S, He H, Ganapathi R, Delahunt B, Magi-Galluzzi C, Zhou M. Clear cell tubulopapillary renal cell carcinoma: a study of 36 distinctive low-grade epithelial tumors of kidney. Am J Surg Pathol 2010:34:1608-1621 
5. Rohan SM, Xiao Y, Liang Y, Dudas ME, Al-Ahmadie HA, Fine SW, Gopalan A, Reuter VE, Rosenblum MK, Russo P, Tickoo SK. Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel-Lindau gene and hypoxia-inducible factor pathway-related proteins. Mod Pathol 2011:24: 1207-1220 
6. Adam J, Couturier J, Molinie V, Vieillefond A, Sibony M.Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumour and a comparative genomic hybridization array study of seven cases. Histopathology 2011:58:1064-1071

 

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KIDNEY ALLOGRAFT PATHOLOGY: FROM MORPHOLOGY TO FUNCTION

Heinz Regele

 Department of Pathology, Innsbruck Medical University, Innsbruck, Austria

 Histologic assessment of allograft biopsies is still the gold standard for typing and grading renal allograft rejection episodes. The technology employed for biopsy assessment and the resulting diagnostic classification did however not always keep pace with the rapidly evolving knowledge about the immune mechanisms of rejection. Since accurate recognition of these mechanisms is crucial for specific therapy and reliable risk assessment, it is mandatory to constantly adjust our diagnostic standards to current immunological knowledge. The introduction of antibody mediated rejection (ABMR) as a diagnostic category a few years ago exemplifies the importance of defining renal allograft rejection according to the prevailing immune mechanism. Although it is generally accepted that donor specific antibodies (DSA) (anti-HLA or anti-ABO) are the main driving force in ABMR, the exact mechanisms of tissue injury are still not completely understood. Binding of DSA to endothelial cells (EC) of the graft followed by complement activation on EC is obviously essential for ABMR. The sequence of subsequent molecular events, mediating severe graft injury, is less well established. The traditional view is that EC damage is directly mediated by antibodies/complement (via generation of C5b-9). This concept was however challenged by our analysis of the transcriptional response of EC (from kidney donors) to complement activation induced by in vitro incubation of EC with DSA. Despite complete activation of complement (including formation of C5b-9), we did not observe any response of EC at the transcriptional level within 24 hours after treatment. This was a surprising finding that however is in line with the lack of early EC injury or signs of acute rejection in experimental models of ABMR induced by injection of anti-MHC antibodies directed at allografts to RAG-2 knockout mice that are devoid of T- and B-cells. In my talk, I will discuss novel concepts arising from observations in renal allograft biopsies and experimental models with specific focus on the mechanisms of endothelial injury in antibody mediated renal allograft rejection.

 

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ZOOBIQUITY^® IN RENAL PATHOLOGY: ANIMAL AND HUMAN INTERFACE

Suzana Tkalčić

Western University of Health Sciences, College of Veterinary Medicine, Pomona, California, USA

Zoobiquity is an initiative from the human medicine side to bypass the boundaries between human and veterinary medicine, and to look closer into the scientific and medical data from the veterinary field in order to find commonalities and solutions for the challenges of the modern medicine. It is a response to an old plea for collaboration from veterinary side that finally became recognized when Dr. Barbara Natterson-Horowitz from UCLA started to apply comparative medicine approach as a consultant on non-human primate cardiology issues with the Los Angeles Zoo. Zoobiquity presents comparative medicine as translational science, where scientific data and experiences from veterinary medicine, comparative biology, molecular biology, and evolutionary sciences, in a context of modern environmental and societal challenges are brought to the clinical practice. It addresses different physical and behavioral health problems (issues like obesity, diabetes, addition, sexually transmitted diseases, OCD, zoonoses, etc.) with an integrated interdisciplinary and inter-professional approach. As such, it is a complementary initiative to a global trend in One Health. When it comes to renal pathology in domestic and wild animals, comparative pathology offers a valuable insight into health status of the world around us. Reactive renal amyloidosis in Abessynian cats and Shar-Pei dogs is a genetic trait with a recognizable histopathologic presentation, while in cattle comes mostly associated with chronic infectious disease. Polycystic kidney disease is inherited as an autosomal dominant trait in Persian cats and bull terriers, pigs and lambs, while in some dog breeds is inherited along with cystic biliary disease. From the zoonotic aspect, besides in dogs and food animals, leptospirosis presented as acute tubulointerstitial nephritis is becoming an important emerging infection in marine mammals and captive wildlife. Greyhound dogs occasionally present with a disease named Alabama Rot, which presents as hemolytic uremic syndrome. Neoplastic diseases of animals also parallel many of human: from nephroblastomas to carcinomas and lymphomas. Iatrogenically, prolonged use of NSAIDs results in acute renal failure due to severe tubular/papillary necrosis in horses and dogs. From the aspect of environmental safety, nephrotoxic compounds like arsenic, lead, cadmium, or mercury cause acute tubular necrosis. Recent worldwide food safety incident with melamine toxicity resulted in renal failure in many Chinese children and mortality of dogs and cats due to its presence in commercial pet food. Food-borne illnesses, like verotoxin producing E. coli O157:H7, also warrant a close interaction between human and veterinary medicine, regardless if the veterinary side presents with animals as non-symptomatic carriers, clinically sick animals with similar pathology, or animals as models for human illness.